Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression

Astrid Boeck, Bo Young Ahn, Charlotte D’Mello, Xueqing Lun, Shyam V. Menon, Mana M. Alshehri, Frank Szulzewsky, Yaoqing Shen, Lubaba Khan, Ngoc Ha Dang, Elliott Reichardt, Kimberly-Ann Goring, Jennifer King, Cameron J. Grisdale, Natalie Grinshtein, Dolores Hambardzumyan, Karlyne M. Reilly, Michael D. Blough, J. Gregory Cairncross, V. Wee Yong, Marco A. Marra, Steven J. M. Jones, David R. Kaplan, Kathy D. McCoy, Eric C. Holland, Pinaki Bose, Jennifer A. Chan, Stephen M. Robbins () and Donna L. Senger ()
Additional contact information
Astrid Boeck: University of Calgary
Bo Young Ahn: University of Calgary
Charlotte D’Mello: University of Calgary
Xueqing Lun: University of Calgary
Shyam V. Menon: University of Calgary
Mana M. Alshehri: University of Calgary
Frank Szulzewsky: Fred Hutchinson Cancer Research Center
Yaoqing Shen: British Columbia Cancer Agency
Lubaba Khan: University of Calgary
Ngoc Ha Dang: University of Calgary
Elliott Reichardt: University of Calgary
Kimberly-Ann Goring: University of Calgary
Jennifer King: University of Calgary
Cameron J. Grisdale: British Columbia Cancer Agency
Natalie Grinshtein: University of Toronto and Program in Neurosciences and Mental Health, Hospital for Sick Children
Dolores Hambardzumyan: Icahn School of Medicine at Mount Sinai
Karlyne M. Reilly: National Cancer Institute
Michael D. Blough: University of Calgary
J. Gregory Cairncross: University of Calgary
V. Wee Yong: University of Calgary
Marco A. Marra: British Columbia Cancer Agency
Steven J. M. Jones: British Columbia Cancer Agency
David R. Kaplan: University of Toronto and Program in Neurosciences and Mental Health, Hospital for Sick Children
Kathy D. McCoy: University of Calgary
Eric C. Holland: Fred Hutchinson Cancer Research Center
Pinaki Bose: University of Calgary
Jennifer A. Chan: University of Calgary
Stephen M. Robbins: University of Calgary
Donna L. Senger: University of Calgary

Nature Communications, 2020, vol. 11, issue 1, 1-24

Abstract: Abstract Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18569-4

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DOI: 10.1038/s41467-020-18569-4

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